Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/ motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface-and are precisely equidistant-from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.key assumption in neuroscience is that the topographical structure of the cerebral cortex provides an organizing principle that constrains its cognitive processes. Recent advances in the field of human connectomics have revealed multiple largescale networks (1-3), each characterized by distinct functional profiles (4). Some are related to basic primary functions, such as movement or perceiving sounds and images; some serve welldocumented, domain-general functions, such as attention or cognitive control (5-8); and some have functional characteristics that remain less well-understood, such as the default-mode network (DMN) (9, 10). Although the topography of these distinct distributed networks has been described using multiple methods (1-3), the reason for their particular spatial relationship and how this constrains their function remain unclear.Advances in mapping local processing streams have revealed spatial gradients that support increasingly abstract levels of representation, often extending along adjacent cortical regions in a stepwise manner (11). In the visual domain, for example, the ventral occipitotemporal object stream transforms simple visual features, coded by neurons in primary visual cortex, into more complex visual descriptions of objects in anterior inferior temporal cortical regions and ultimately, contributes to multimodal semantic representations in the middle temporal cortex and the most anterior temporal cortex that capture the meaning of what we see, hear, and do (12)(13)(14)(15). Similarly, in the prefrontal cortex, a rostral-caudal gradient has been proposed, whereby goals become increasingly abstract in anterior areas more distant from motor cortex...

Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative  T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo.

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution – even within subnetworks.